I. Field of the Invention
The invention generally concerns the fields of medicine and molecular biology. In particular, the invention concerns polypeptides for delivery of therapeutic molecules method for the use thereof.
II. Description of Related Art
In the past, therapeutic compositions have generally been delivered by passive or nonspecific targeting. Passive targeting includes targeting based upon size, ionic state, and biological factors and is limited the ability of the therapeutic to diffuse to its site action and the rate of clearance for the therapeutic. Intravenously injected molecules, for example, may have to traverse a cell membrane to reach a site of action and may be readily processed or degraded by the body, thus limiting the use of many therapeutics. To address this issue, synthetic polymers such as poly(N-isopropylacrylamide) (Schild, 1992), poly(ethylene glycol)-block-poly(caprolactone) copolymers (Kim et al., 2004), poly(ethylene oxide)-poly(propylene oxide) multiblock copolymers (Sosnik and Cohn, 2005), and multiple hydrogen bonding-poly(butylenes terephthalate) (Yamauchi et al., 2004) have been used as monolithic gels to deliver drugs. Unfortunately, synthetic polymers such as these suffer from the effects of polydispersity, lack of architectural control, variable levels of biocompatibility, and complex synthesis schemes.
Thus, on merely a biophysical basis, genetically engineered biopolymers such as elastin-like polymers (ELP) pose an attractive alternative to traditional polymer macromolecules for gene and drug delivery due to their monodispersity, non-immunogenicity, and unparalleled control of architecture and biophysical characteristics (“smart” polymer behaviors, ionization state, hydrophobicity). Genetic engineering confers precise control of the biophysical characteristics of biopolymers, a level of control yet to be realized in synthetic polymer syntheses. Through molecular biology techniques, the pentapeptide sequence, molecular weight, and architecture of the ELP can be precisely controlled for subsequent an purified as a recombinant polypeptide, resulting in monodisperse, non-immunogenic (Urry et al., 1991) ELP biopolymers with variable ionic and hydrophobicity characteristics. Traditional synthetic polymers lack this degree of molecular weight control and viral gene carriers suffer from intrinsic immunogenicity; therefore, there is significant promise for the use of genetically engineered polymers in gene and drug delivery (Kopecek, 2003).
Genetically engineered biopolymers show great promise as macromolecule, gene and drug carriers due to genetic control of composition and monodispersity. Moreover, elastin-like polymers are thermosensitive enabling methods for hyperthermic targeting to specific sites for therapy. The use of ELP-biomacromolecules-ELP biopolymers for the delivery of drugs (Dreher et al., 2003; Herrero-Vanrell et al., 2005) and peptides (Bidwell and Raucher, 2005) has been reported. However, previously there has not been a effective ELP platform that could be used to deliver the array of therapies currently in use in the medical field.